Mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 occur at an exceptionally high frequency (80%) in gliomas. The mutations also present in 23% of acute myeloid leukemia, and are rarely observed in other types of cancers. The frequency, specificity, and early timing of IDH mutations provide strong evidence for their importance in tumorigenesis, prognosis and therapeutics. However, the functional effects and significance of IDH mutations in human cancer have not been fully defined. Currently, a major limitation of the field is that there are no cell line models which recapitulate IDH mutation-dependent tumor progression.